Hello, I work in a lab that researches biopesticides in the form of insect neuropeptides, which bind to receptor proteins. I am trying to use ChimeraX to model potential binding sites between peptide ligands and their corresponding receptor. Does ChimeraX have this capability? When I was trying to figure this out myself online through the ChimeraX Youtube tutorials and tutorials on the UCSF site, I came across a comment on a video that mentioned I could upload the sequences of my receptor and peptide ligand separated by a comma, and model it as a protein complex, and then I can get information on where the two molecules interact. I’m relatively new to protein research, and so I hadn’t yet thought of ligand-protein interactions as a type of protein complex. My specific questions are:

· When modeling a peptide ligand and a receptor as a protein complex, will ChimeraX accurately predict the relationship between the two molecules based on binding compatibility? Or is it based on something else, like similarity of sequence alignments…?

· If multiple binding sites are possible, is there any way to view the different options for multiple binding sites? Or is there any way to restrict the area on the receptor to which my target peptide ligand is predicted to bind (i.e. the extracellular region only)?

· The peptide ligands are only 7-9 amino acids in length and do not take very long to model, but the receptor is about 600 amino acids and takes a much longer time to model. Do I have to model protein complexes by re-modeling everything for each different receptor-ligand combination, or can I combine existing models somehow?

I hope these questions aren’t too troublesome, and I hope I haven’t grossly misunderstood ChimeraX’s capabilities.

Thank you for your time,

Ryssa Parks